Intracellular signalling Flashcards
What are the different ways in which signals can be integrated?
- 1 receptor → multiple pathways (divergence)
- 2 receptors → same pathway (convergence)
- different receptors → multiple pathways (that cross over & affect the other)
What are the main “player” pathways in every cell?
cAMP, Ras, Raf and MAP Kinase pathways
What is the difference between proteins sythesisted on rough ER ribosomes and free ribosomes?
Rough ER ribosomes synthesise membrane-associated proteins
What are the short term effects of intracellular Ca++?
- exocytosis
- contraction
- ion channel regulation
- Ca++ release from ER
What are the short term effects of intracellular Ca++?
- exocytosis
- contraction
- ion channel regulation
- Ca++ release from ER
What are the mid term effects of intracellular Ca++?
- regulate energy production in mitochondria
What are the long term effects of intracellular Ca++?
- reach nucleus & regulate gene expression
- reach ER & regulate protein syntehsis and folding
What is the comparative concentrations of Ca++ in the cytosol vs ER?
- cytosol 50-100nM
- ER 100-800 µM
*(ER 4 order of magnitude higher than cytosol)
what is the distribution of ER within a neuron?
The ER is a continuous membrane persisting through the entire cell and into around 50% of dendritic spines. In some areas it is closer to the membrane than in others.
What are 2 pathways of Ca++ intracellular release?
One:
* signal is received, activates PLC to cleave PIP2 into IP3 & DAG
* IP3 travels to ER & binds IP3R
* IP3R activation leads to release of Ca++ from ER lumen
Two:
* Ca++ enters via voltage channel
* activates Ryanodine receptor (RYR)
* RYR activation leads to release of Ca++ from ER lumen
What are the 2 receptors on ER that lead to Ca++ release
IP3
RYR
How does the ER act as both a Ca++ source and sink?
It acts as a source by releasing Ca++ when it is needed in the cell
It acts as a sink by transporting Ca++ in when cytosol [Ca++] is too high
How does the ER act as both a Ca++ source and sink?
It acts as a source by releasing Ca++ when it is needed in the cell
It acts as a sink by transporting Ca++ in when cytosol [Ca++] is too high
What is the luminal loading?
the amount of calcium inside the ER lumen available to be released
What control the excitability of the ER as a calcium source?
the degree of luminal loading. the more Ca++ in the lumen, the easier to generate a response
What is calcium-induced-calcium response?
A small amount of calcium release further promotes more calcium release, in a wave or oscillation.
What is the store loading model for Ca++ oscillation?
that the loading (refilling) of the ER Ca++ store controls the timing of Ca++ oscillations because it determines the sensitivity of the IP3 receptors to control when the next spike it
How does store loading impact oscillation frequency?
how quickly the ER is refilled determines how quickly another signal can be generated (if ER is full, easier to generate signal. if ER empty, harder to generate signal)
How does store loading impact oscillation frequency?
how quickly the ER is refilled determines how quickly another signal can be generated (if ER is full, easier to generate signal. if ER empty, harder to generate signal)
How do NTs/hormones modulate the oscillation?
When NT or hormones bind, they cause either ↑IP3 or ↑Ca++, both of which induce Ca++ release and the CICR.
What controls the magnitude of the Ca++ wave?
The degree of store loading and IP3 concentration
What is the meaning of the neuron-within-a-neuron concept?
The ER represents another layer inside the cell that manages intracellular processes.
Where the plasma membrane mediates neuron response to the outside world, ER membrane mediates neuron response inside the cell.
What is the meaning of the neuron-within-a-neuron concept?
The ER represents another layer inside the cell that manages intracellular processes.
Where the plasma membrane mediates neuron response to the outside world, ER membrane mediates neuron response inside the cell.
Compare signal integration of ER & plasma membrane
ER: second messengers (Ca++, IP3)
Plasma membrane: + and - neural inputs
Compare regenerative processes of ER and plasma membrane
ER: Ca++ waves
Plasma membrane: AP
compare speed/mechanism of propagation in ER vs plasma membrane:
ER: Slow, propagation by Ca++ diffusion
Plasma membrane: fast, propagation by local circuits
Compare conduction systems of ER and plasma membrane
ER: IP3Rs and RyRs
Plasma Membrane: VGSCs & VGCCs
Describe reciprocal interactions between ER & plasma membrane
the ER Ca++ release modulates neuron excitability. Ca++ entry through membrane sensitises ER Ca++ release
How is Ca++ involved in neuron excitability?
Ca++ activates K+ channels that work to restore the resting membrane potential after depolarisation
How is Ca++ involved in synaptic plasticity?
Ca++ release modulates both long-term potentiation and long-term depression, but we dont understand exactly how.
How is Ca++ involved in gene transcription?
Ca++ can enter the nucleus and activate CREB protein, which is a transcription factor that binds to DNA and regulates the transcription of specific genes
What is the implication of Ca++ deregulation in context of neurodegenerative diseases?
Neurodegenerative diseases (AD, PD, HD) can impact membrane proteins and result in Ca++ overload (too much intracellular Ca++).
This intereferes with mitochondria ETC, the cell cannot supply energy for activity, and leads to cell death
What is intracellular signal transduction?
A chain of reactions that transmit signals from the cell surface to a variety of intracellular targets.
